Abstract: Data regarding clinical outcomes after intravascular imaging–guided percutaneous coronary intervention (PCI) for complex coronary-artery lesions, as compared with outcomes after angiography-guided PCI, are limited. Download a PDF of the Research Summary. In this prospective, multicenter, open-label trial in South Korea, we randomly assigned patients with complex coronary-artery lesions in a 2:1 ratio to undergo either intravascular imaging–guided PCI or angiography-guided PCI. In the intravascular imaging group, the choice between intravascular ultrasonography and optical coherence tomography was at the operators’ discretion. The primary end point was a composite of death from cardiac causes, target-vessel–related myocardial infarction, or clinically driven target-vessel revascularization. Safety was also assessed. A total of 1639 patients underwent randomization, with 1092 assigned to undergo intravascular imaging–guided PCI and 547 assigned to undergo angiography-guided PCI. At a median follow-up of 2.1 years (interquartile range, 1.4 to 3.0), a primary end-point event had occurred in 76 patients (cumulative incidence, 7.7%) in the intravascular imaging group and in 60 patients (cumulative incidence, 12.3%) in the angiography group (hazard ratio, 0.64; 95% confidence interval, 0.45 to 0.89; P=0.008). Death from cardiac causes occurred in 16 patients (cumulative incidence, 1.7%) in the intravascular imaging group and in 17 patients (cumulative incidence, 3.8%) in the angiography group; target-vessel–related myocardial infarction occurred in 38 (cumulative incidence, 3.7%) and 30 (cumulative incidence, 5.6%), respectively; and clinically driven target-vessel revascularization in 32 (cumulative incidence, 3.4%) and 25 (cumulative incidence, 5.5%), respectively. There were no apparent between-group differences in the incidence of procedure-related safety events. Among patients with complex coronary-artery lesions, intravascular imaging–guided PCI led to a lower risk of a composite of death from cardiac causes, target-vessel–related myocardial infarction, or clinically driven target-vessel revascularization than angiography-guided PCI. (Supported by Abbott Vascular and Boston Scientific; RENOVATE-COMPLEX-PCI ClinicalTrials.gov number, NCT03381872). QUICK TAKE VIDEO SUMMARYImaging- or Angiography-Guided PCI 02:11

Abstract: Pembrolizumab and pembrolizumab-chemotherapy demonstrated efficacy in recurrent/metastatic head and neck squamous cell carcinoma in KEYNOTE-048. Post hoc analysis of long-term efficacy and progression-free survival on next-line therapy (PFS2) is presented.Patients were randomly assigned (1:1:1) to pembrolizumab, pembrolizumab-chemotherapy, or cetuximab-chemotherapy. Efficacy was evaluated in programmed death ligand 1 (PD-L1) combined positive score (CPS) ≥ 20, CPS ≥ 1, and total populations, with no multiplicity or alpha adjustment.The median study follow-up was 45.0 months (interquartile range, 41.0-49.2; n = 882). At data cutoff (February 18, 2020), overall survival improved with pembrolizumab in the PD-L1 CPS ≥ 20 (hazard ratio [HR], 0.61; 95% CI, 0.46 to 0.81) and CPS ≥ 1 populations (HR, 0.74; 95% CI, 0.61 to 0.89) and was noninferior in the total population (HR, 0.81; 95% CI, 0.68 to 0.97). Overall survival improved with pembrolizumab-chemotherapy in the PD-L1 CPS ≥ 20 (HR, 0.62; 95% CI, 0.46 to 0.84), CPS ≥ 1 (HR, 0.64; 95% CI, 0.53 to 0.78), and total (HR, 0.71; 95% CI, 0.59 to 0.85) populations. The objective response rate on second-course pembrolizumab was 27.3% (3 of 11). PFS2 improved with pembrolizumab in the PD-L1 CPS ≥ 20 (HR, 0.64; 95% CI, 0.48 to 0.84) and CPS ≥ 1 (HR, 0.79; 95% CI, 0.66 to 0.95) populations and with pembrolizumab-chemotherapy in the PD-L1 CPS ≥ 20 (HR, 0.64; 95% CI, 0.48 to 0.86), CPS ≥ 1 (HR, 0.66; 95% CI, 0.55 to 0.81), and total (HR, 0.73; 95% CI, 0.61 to 0.88) populations. PFS2 was similar after pembrolizumab and longer after pembrolizumab-chemotherapy on next-line taxanes and shorter after pembrolizumab and similar after pembrolizumab-chemotherapy on next-line nontaxanes.With a 4-year follow-up, first-line pembrolizumab and pembrolizumab-chemotherapy continued to demonstrate survival benefit versus cetuximab-chemotherapy in recurrent/metastatic head and neck squamous cell carcinoma. Patients responded well to subsequent treatment after pembrolizumab-based therapy.

Abstract: Background: Pulsed field ablation is a novel nonthermal cardiac ablation modality using ultra-rapid electrical pulses to cause cell death by a mechanism of irreversible electroporation. Unlike the traditional ablation energy sources, pulsed field ablation has demonstrated significant preferentiality to myocardial tissue ablation, and thus avoids certain thermally mediated complications. However, its safety and effectiveness remain unknown in usual clinical care. Methods: MANIFEST-PF (Multi-National Survey on the Methods, Efficacy, and Safety on the Post-Approval Clinical Use of Pulsed Field Ablation) is a retrospective, multinational, patient-level registry wherein patients at each center were prospectively included in their respective center registries. The registry included all patients undergoing postapproval treatment with a multielectrode 5-spline pulsed field ablation catheter to treat atrial fibrillation (AF) between March 1, 2021, and May 30, 2022. The primary effectiveness outcome was freedom from clinical documented atrial arrhythmia (AF/atrial flutter/atrial tachycardia) of ≥30 seconds on the basis of electrocardiographic data after a 3-month blanking period (on or off antiarrhythmic drugs). Safety outcomes included the composite of acute (<7 days postprocedure) and latent (>7 days) major adverse events. Results: At 24 European centers (77 operators) pulsed field ablation was performed in 1568 patients with AF: age 64.5±11.5 years, female 35%, paroxysmal/persistent AF 65%/32%, CHA 2 DS 2 -VASc 2.2±1.6, median left ventricular ejection fraction 60%, and left atrial diameter 42 mm. Pulmonary vein isolation was achieved in 99.2% of patients. After a median (interquartile range) follow-up of 367 (289–421) days, the 1-year Kaplan-Meier estimate for freedom from atrial arrhythmia was 78.1% (95% CI, 76.0%–80.0%); clinical effectiveness was more common in patients with paroxysmal AF versus persistent AF (81.6% versus 71.5%; P =0.001). Acute major adverse events occurred in 1.9% of patients. Conclusions: In this large observational registry of the postapproval clinical use of pulsed field technology to treat AF, catheter ablation using pulsed field energy was clinically effective in 78% of patients with AF.

Abstract: European data pre-2019 suggest statin monotherapy is the most common approach to lipid management for preventing cardiovascular (CV) events, resulting in only one-fifth of high- and very high-risk patients achieving the 2019 ESC/EAS recommended low-density lipoprotein cholesterol (LDL-C) goals. Whether the treatment landscape has evolved, or gaps persist remains of interest.Baseline data are presented from SANTORINI, an observational, prospective study that documents the use of lipid-lowering therapies (LLTs) in patients ≥18 years at high or very high CV risk between 2020 and 2021 across primary and secondary care settings in 14 European countries.Of 9602 enrolled patients, 9044 with complete data were included (mean age: 65.3 ± 10.9 years; 72.6% male). Physicians reported using 2019 ESC/EAS guidelines as a basis for CV risk classification in 52.0% (4706/9044) of patients (overall: high risk 29.2%; very high risk 70.8%). However, centrally re-assessed CV risk based on 2019 ESC/EAS guidelines suggested 6.5% (308/4706) and 91.0% (4284/4706) were high- and very high-risk patients, respectively. Overall, 21.8% of patients had no documented LLTs, 54.2% were receiving monotherapy and 24.0% combination LLT. Median (interquartile range [IQR]) LDL-C was 2.1 (1.6, 3.0) mmol/L (82 [60, 117] mg/dL), with 20.1% of patients achieving risk-based LDL-C goals as per the 2019 ESC/EAS guidelines.At the time of study enrolment, 80% of high- and very high-risk patients failed to achieve 2019 ESC/EAS guidelines LDL-C goals. Contributory factors may include CV risk underestimation and underutilization of combination therapies. Further efforts are needed to achieve current guideline-recommended LDL-C goals.ClinicalTrials.gov Identifier: NCT04271280.This study is funded by Daiichi Sankyo Europe GmbH, Munich, Germany.

Abstract: Several studies have suggested that patients with kidney failure may benefit from high-dose hemodiafiltration as compared with standard hemodialysis. However, given the limitations of the various published studies, additional data are needed. We conducted a pragmatic, multinational, randomized, controlled trial involving patients with kidney failure who had received high-flux hemodialysis for at least 3 months. All the patients were deemed to be candidates for a convection volume of at least 23 liters per session (as required for high-dose hemodiafiltration) and were able to complete patient-reported outcome assessments. The patients were assigned to receive high-dose hemodiafiltration or continuation of conventional high-flux hemodialysis. The primary outcome was death from any cause. Key secondary outcomes were cause-specific death, a composite of fatal or nonfatal cardiovascular events, kidney transplantation, and recurrent all-cause or infection-related hospitalizations. A total of 1360 patients underwent randomization: 683 to receive high-dose hemodiafiltration and 677 to receive high-flux hemodialysis. The median follow-up was 30 months (interquartile range, 27 to 38). The mean convection volume during the trial in the hemodiafiltration group was 25.3 liters per session. Death from any cause occurred in 118 patients (17.3%) in the hemodiafiltration group and in 148 patients (21.9%) in the hemodialysis group (hazard ratio, 0.77; 95% confidence interval, 0.65 to 0.93). In patients with kidney failure resulting in kidney-replacement therapy, the use of high-dose hemodiafiltration resulted in a lower risk of death from any cause than conventional high-flux hemodialysis. (Funded by the European Commission Research and Innovation; CONVINCE Dutch Trial Register number, NTR7138.)

Abstract: PURPOSE Limited prospective data are available on sequential immunotherapy and BRAF/MEK inhibition for BRAFV600-mutant metastatic melanoma. METHODS SECOMBIT is a randomized, three-arm, noncomparative phase II trial (ClinicalTrials.gov identifier: NCT02631447 ). Patients with untreated, metastatic BRAFV600-mutant melanoma from 37 sites in nine countries were randomly assigned to arm A (encorafenib [450 mg orally once daily] plus binimetinib [45 mg orally twice daily] until progressive disease [PD] -> ipilimumab plus nivolumab [ipilimumab 3 mg/kg once every 3 weeks and nivolumab 1 mg/kg once every 3 weeks × four cycles -> nivolumab 3 mg/kg every 2 weeks]), arm B [ipilimumab plus nivolumab until PD -> encorafenib plus binimetinib], or arm C (encorafenib plus binimetinib for 8 weeks -> ipilimumab plus nivolumab until PD -> encorafenib plus binimetinib). The primary end point was overall survival (OS) at 2 years. Secondary end points included total progression-free survival, 3-year OS, best overall response rate, duration of response, and biomarkers in the intent-to-treat population. Safety was analyzed throughout sequential treatment in all participants who received at least one dose of study medication. RESULTS A total of 209 patients were randomly assigned (69 in arm A, 71 in arm B, and 69 in arm C). At a median follow-up of 32.2 (interquartile range, 27.9-41.6) months, median OS was not reached in any arm and more than 30 patients were alive in all arms. Assuming a null hypothesis of median OS of ≤ 15 months, the OS end point was met for all arms. The 2-year and 3-year OS rates were 65% (95% CI, 54 to 76) and 54% (95% CI, 41 to 67) in arm A, 73% (95% CI, 62 to 84) and 62% (95% CI, 48 to 76) in arm B, and 69% (95% CI, 59 to 80) and 60% (95% CI, 58 to 72) in arm C. No new safety signals emerged. CONCLUSION Sequential immunotherapy and targeted therapy provide clinically meaningful survival benefits for patients with BRAFV600-mutant melanoma.

Abstract: Abstract Aims Pulsed field ablation (PFA) is a new, non-thermal ablation modality for pulmonary vein (PV) isolation in patients with atrial fibrillation (AF). The multi-centre EUropean Real World Outcomes with Pulsed Field AblatiOn in Patients with Symptomatic AtRIAl Fibrillation (EU-PORIA) registry sought to determine the safety, efficacy, and learning curve characteristics for the pentaspline, multi-electrode PFA catheter. Methods and results All-comer AF patients from seven high-volume centres were consecutively enrolled. Procedural and follow-up data were collected. Learning curve effects were analysed by operator ablation experience and primary ablation modality. In total, 1233 patients (61% male, mean age 66 ± 11years, 60% paroxysmal AF) were treated by 42 operators. In 169 patients (14%), additional lesions outside the PVs were performed, most commonly at the posterior wall (n = 127). Median procedure and fluoroscopy times were 58 (interquartile range: 40–87) and 14 (9–21) min, respectively, with no differences due to operator experience. Major complications occurred in 21/1233 procedures (1.7%) including pericardial tamponade (14; 1.1%) and transient ischaemic attack or stroke (n = 7; 0.6%), of which one was fatal. Prior cryoballoon users had less complication. At a median follow-up of 365 (323–386) days, the Kaplan–Meier estimate of arrhythmia-free survival was 74% (80% for paroxysmal and 66% for persistent AF). Freedom from arrhythmia was not influenced by operator experience. In 149 (12%) patients, a repeat procedure was performed due to AF recurrence and 418/584 (72%) PVs were durably isolated. Conclusion The EU-PORIA registry demonstrates a high single-procedure success rate with an excellent safety profile and short procedure times in a real-world, all-comer AF patient population.

Abstract: BACKGROUND Efanesoctocog alfa provides high sustained factor VIII activity by overcoming the von Willebrand factor-imposed half-life ceiling. The efficacy, safety, and pharmacokinetics of efanesoctocog alfa for prophylaxis and treatment of bleeding episodes in previously treated patients with severe hemophilia A are unclear. METHODS We conducted a phase 3 study involving patients 12 years of age or older with severe hemophilia A. In group A, patients received once-weekly prophylaxis with efanesoctocog alfa (50 IU per kilogram of body weight) for 52 weeks. In group B, patients received on-demand treatment with efanesoctocog alfa for 26 weeks, followed by once-weekly prophylaxis with efanesoctocog alfa for 26 weeks. The primary end point was the mean annualized bleeding rate in group A; the key secondary end point was an intrapatient comparison of the annualized bleeding rate during prophylaxis in group A with the rate during prestudy factor VIII prophylaxis. Additional end points included treatment of bleeding episodes, safety, pharmacokinetics, and changes in physical health, pain, and joint health. RESULTS In group A (133 patients), the median annualized bleeding rate was 0 (interquartile range, 0 to 1.04), and the estimated mean annualized bleeding rate was 0.71 (95% confidence interval [CI], 0.52 to 0.97). The mean annualized bleeding rate decreased from 2.96 (95% CI, 2.00 to 4.37) to 0.69 (95% CI, 0.43 to 1.11), a finding that showed superiority over prestudy factor VIII prophylaxis (P<0.001). A total of 26 patients were enrolled in group B. In the overall population, nearly all bleeding episodes (97%) resolved with one injection of efanesoctocog alfa. Weekly prophylaxis with efanesoctocog alfa provided mean factor VIII activity of more than 40 IU per deciliter for the majority of the week and of 15 IU per deciliter at day 7. Prophylaxis with efanesoctocog alfa for 52 weeks (group A) improved physical health (P<0.001), pain intensity (P = 0.03), and joint health (P = 0.01). In the overall study population, efanesoctocog alfa had an acceptable side-effect profile, and the development of inhibitors to factor VIII was not detected. CONCLUSIONS In patients with severe hemophilia A, once-weekly efanesoctocog alfa provided superior bleeding prevention to prestudy prophylaxis, normal to near-normal factor VIII activity, and improvements in physical health, pain, and joint health. (Funded by Sanofi and Sobi; XTEND-1 ClinicalTrials.gov number, NCT04161495.).

Abstract: Rationale: Shared symptoms and genetic architecture between coronavirus disease (COVID-19) and lung fibrosis suggest severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may lead to progressive lung damage. Objectives: The UK Interstitial Lung Disease Consortium (UKILD) post–COVID-19 study interim analysis was planned to estimate the prevalence of residual lung abnormalities in people hospitalized with COVID-19 on the basis of risk strata. Methods: The PHOSP–COVID-19 (Post-Hospitalization COVID-19) study was used to capture routine and research follow-up within 240 days from discharge. Thoracic computed tomography linked by PHOSP–COVID-19 identifiers was scored for the percentage of residual lung abnormalities (ground-glass opacities and reticulations). Risk factors in linked computed tomography were estimated with Bayesian binomial regression, and risk strata were generated. Numbers within strata were used to estimate posthospitalization prevalence using Bayesian binomial distributions. Sensitivity analysis was restricted to participants with protocol-driven research follow-up. Measurements and Main Results: The interim cohort comprised 3,700 people. Of 209 subjects with linked computed tomography (median, 119 d; interquartile range, 83–155), 166 people (79.4%) had more than 10% involvement of residual lung abnormalities. Risk factors included abnormal chest X-ray (risk ratio [RR], 1.21; 95% credible interval [CrI], 1.05–1.40), percent predicted DlCO less than 80% (RR, 1.25; 95% CrI, 1.00–1.56), and severe admission requiring ventilation support (RR, 1.27; 95% CrI, 1.07–1.55). In the remaining 3,491 people, moderate to very high risk of residual lung abnormalities was classified at 7.8%, and posthospitalization prevalence was estimated at 8.5% (95% CrI, 7.6–9.5), rising to 11.7% (95% CrI, 10.3–13.1) in the sensitivity analysis. Conclusions: Residual lung abnormalities were estimated in up to 11% of people discharged after COVID-19–related hospitalization. Health services should monitor at-risk individuals to elucidate long-term functional implications.

Abstract: The Environmental influences on Child Health Outcomes (ECHO)-wide Cohort Study (EWC), a collaborative research design comprising 69 cohorts in 31 consortia, was funded by the National Institutes of Health (NIH) in 2016 to improve children's health in the United States. The EWC harmonizes extant data and collects new data using a standardized protocol, the ECHO-wide Cohort data Collection Protocol (EWCP). EWCP visits occur at least once per life stage, but the frequency and timing of the visits vary across cohorts. As of March 4, 2022, the EWC cohorts contributed data from 60,553 children and consented 29,622 children for new EWCP data and biospecimen collection. The median (interquartile range) age of EWCP-enrolled children was 7.5 years (3.7-11.1). Surveys, interviews, standardized examinations, laboratory analyses, and medical record abstraction are used to obtain information in five main outcome areas: pre-, peri-, and post-natal outcomes; neurodevelopment; obesity; airways; and positive health. Exposures include place- (e.g., air pollution, neighborhood socioeconomic status), family- (e.g., parental mental health), and individual-level (e.g., diet, genomics) factors.

Abstract: Approximately 20% of patients with chronic limb-threatening ischemia have no revascularization options, leading to above-ankle amputation. Transcatheter arterialization of the deep veins is a percutaneous approach that creates an artery-to-vein connection for delivery of oxygenated blood by means of the venous system to the ischemic foot to prevent amputation. Download a PDF of the Research Summary. We conducted a prospective, single-group, multicenter study to evaluate the effect of transcatheter arterialization of the deep veins in patients with nonhealing ulcers and no surgical or endovascular revascularization treatment options. The composite primary end point was amputation-free survival (defined as freedom from above-ankle amputation or death from any cause) at 6 months, as compared with a performance goal of 54%. Secondary end points included limb salvage, wound healing, and technical success of the procedure. We enrolled 105 patients who had chronic limb-threatening ischemia and were of a median age of 70 years (interquartile range, 38 to 89). Of the patients enrolled, 33 (31.4%) were women and 45 (42.8%) were Black, Hispanic, or Latino. Transcatheter arterialization of the deep veins was performed successfully in 104 patients (99.0%). At 6 months, 66.1% of the patients had amputation-free survival. According to Bayesian analysis, the posterior probability that amputation-free survival at 6 months exceeded a performance goal of 54% was 0.993, which exceeded the prespecified threshold of 0.977. Limb salvage (avoidance of above-ankle amputation) was attained in 67 patients (76.0% by Kaplan–Meier analysis). Wounds were completely healed in 16 of 63 patients (25%) and were in the process of healing in 32 of 63 patients (51%). No unanticipated device-related adverse events were reported. We found that transcatheter arterialization of the deep veins was safe and could be performed successfully in patients with chronic limb-threatening ischemia and no conventional surgical or endovascular revascularization treatment options. (Funded by LimFlow; PROMISE II study ClinicalTrials.gov number, NCT03970538.) QUICK TAKE VIDEO SUMMARYTranscatheter Arterialization of Veins for Limb Ischemia 02:19

Abstract: The impact of diagnostic delay on the clinical course of inflammatory bowel disease (IBD) remains uncertain.

Abstract: Weight regain after bariatric surgery occurs in up to a third of patients and reduces treatment-associated health benefits. The efficacy of glucagon-like peptide-1 receptor agonists (GLP1-RA) for treatment of type 2 diabetes mellitus and obesity is well established, but their role in the treatment of weight regain after bariatric surgery remains to be defined.This was a single centre retrospective observational study conducted at a Swiss bariatric reference centre. Patients with 6 months of treatment with GLP1-RA, up until November 2021, due to weight regain after bariatric surgery were identified. Data on body weight and relevant clinical parameters were collected before and after 6 months of treatment with GLP1-RA. Data are presented as median (interquartile range).Fifty patients (82% female) were included. Before GLP1-RA treatment (liraglutide, n=29; semaglutide, n=21), weight and BMI were 90.5 kg (83.4, 107.9) and 34.0 kg/m2 (31.7, 38.7), respectively, with a post-bariatric weight regain of 15.1% (10.6, 22.8) of total body weight and 4.6 kg/m2 (3.3, 6.2). After 6 months of GLP1-RA treatment, a reduction in weight and BMI of 8.8% (5.2, 11.4) of total body weight and 2.9 kg/m2 (1.8, 4.0) was observed (P value <0.0001), corresponding to 67.4% (40.4, 92.2) of the weight regain. No serious adverse events were reported.For patients experiencing weight regain after bariatric surgery, two-thirds of the weight regain can be safely lost with GLP1-RA, providing clinicians with a therapeutic option for this clinical challenge, and highlights the need for a large-scale randomized clinical trial.

Abstract: Acute myocardial injury in hospitalized patients with coronavirus disease 2019 (COVID-19) has a poor prognosis. Its associations and pathogenesis are unclear. Our aim was to assess the presence, nature, and extent of myocardial damage in hospitalized patients with troponin elevation.Across 25 hospitals in the United Kingdom, 342 patients with COVID-19 and an elevated troponin level (COVID+/troponin+) were enrolled between June 2020 and March 2021 and had a magnetic resonance imaging scan within 28 days of discharge. Two prospective control groups were recruited, comprising 64 patients with COVID-19 and normal troponin levels (COVID+/troponin-) and 113 patients without COVID-19 or elevated troponin level matched by age and cardiovascular comorbidities (COVID-/comorbidity+). Regression modeling was performed to identify predictors of major adverse cardiovascular events at 12 months.Of the 519 included patients, 356 (69%) were men, with a median (interquartile range) age of 61.0 years (53.8, 68.8). The frequency of any heart abnormality, defined as left or right ventricular impairment, scar, or pericardial disease, was 2-fold greater in cases (61% [207/342]) compared with controls (36% [COVID+/troponin-] versus 31% [COVID-/comorbidity+]; P<0.001 for both). More cases than controls had ventricular impairment (17.2% versus 3.1% and 7.1%) or scar (42% versus 7% and 23%; P<0.001 for both). The myocardial injury pattern was different, with cases more likely than controls to have infarction (13% versus 2% and 7%; P<0.01) or microinfarction (9% versus 0% and 1%; P<0.001), but there was no difference in nonischemic scar (13% versus 5% and 14%; P=0.10). Using the Lake Louise magnetic resonance imaging criteria, the prevalence of probable recent myocarditis was 6.7% (23/342) in cases compared with 1.7% (2/113) in controls without COVID-19 (P=0.045). During follow-up, 4 patients died and 34 experienced a subsequent major adverse cardiovascular event (10.2%), which was similar to controls (6.1%; P=0.70). Myocardial scar, but not previous COVID-19 infection or troponin, was an independent predictor of major adverse cardiovascular events (odds ratio, 2.25 [95% CI, 1.12-4.57]; P=0.02).Compared with contemporary controls, patients with COVID-19 and elevated cardiac troponin level have more ventricular impairment and myocardial scar in early convalescence. However, the proportion with myocarditis was low and scar pathogenesis was diverse, including a newly described pattern of microinfarction.URL: https://www.isrctn.com; Unique identifier: 58667920.

Abstract: The associations between air pollution exposure and morbidity and mortality of cardiovascular diseases (CVDs) have been widely reported; however, evidence on such associations across different dynamic disease trajectories remain unknown.We examined whether ambient air pollution during the prehypertension (pre-HTN) stage could aggravate the progression from hypertension (HTN) to CVD, and consequent death.A total of 168,010 adults with pre-HTN (120-139 mmHg systolic blood pressure or 80-89 mmHg diastolic blood pressure) from the UK Biobank were included in this analysis. We used a multistate model to explore the associations between five air pollutants (PM2.5, PM2.5 absorbance, PM10, NO2, and NOx) and the risk of six disease transitions (from pre-HTN to HTN, from pre-HTN to CVD, from pre-HTN to death, from HTN to CVD, from HTN to death, and from CVD to death). Mediation analyses were further conducted to explore the role of intermediate diseases in the dynamic progression of CVDs.During a median follow-up of 12 y, 13,743 (8.18%) of participants with pre-HTN developed HTN, whereas 12,825 (7.63%) and 4,467 (2.66%) directly developed CVD or died, respectively. Air pollution was positively associated with the dynamic disease progression. For example, a per-interquartile range increase of PM2.5 was significantly associated with the hazard ratios (HRs) of 1.105 [95% confidence intervals (CI): 1.083, 1.127], 1.045 (95% CI: 1.022, 1.068), and 1.086 (95% CI: 1.047, 1.126) in the transition from pre-HTN to HTN, CVD, and death, respectively. Higher levels of air pollution were associated with increased transition probability of disease progression. Mediation analyses indicated that intermediate diseases subsequently significantly mediated air pollutant-associated risk to develop more serious disease.This study provides evidence that air pollution might play a role in the early stages of CVD progression. Controlling air pollution might be an effective measure to prevent CVD progression and reduce the disease burden of CVD. https://doi.org/10.1289/EHP10967.

Abstract: The cryoballoon represents the gold standard single-shot device for pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF). Single-shot pulsed field PVI ablation (nonthermal, cardiac tissue selective) has recently entered the arena. We sought to compare procedural data and long-term outcome of both techniques.Consecutive AF patients who underwent pulsed field ablation (PFA) and cryoballoon-based PVI were enrolled. Cryoballoon PVI was performed using the second-generation 28-mm cryoballoon; PFA was performed using a 31/35-mm pentaspline catheter. Success was defined as no recurrence of atrial tachyarrhythmia after a 3-month blanking period.Four hundred patients were included (56.5% men; 60.8% paroxysmal AF; age, 70 [interquartile range, 59-77] years), 200 in each group (cryoballoon and PFA), and baseline characteristics did not differ. Acute PVI was achieved in 100% of PFA and in 98% (196/200) of cryoballoon patients (P=0.123; 4 touch-up ablations). Median procedure time was significantly shorter in PFA (34.5 [29-40] minutes) versus cryoballoon (50 [45-60] minutes; P<0.001), fluoroscopy time was similar. Overall procedural complications were 6.5% in cryoballoon and 3.0% in PFA (P=0.1), driven by a higher rate of phrenic nerve palsies using cryoballoon. The 1-year success rates in paroxysmal AF (cryoballoon, 83.1%; PFA, 80.3%; P=0.724) and persistent AF (cryoballoon, 71%; PFA, 66.8%; P=0.629) were similar for both techniques.PFA compared with cryoballoon PVI shows a similar procedural efficacy but is associated with shorter procedure time and no phrenic nerve palsies. Importantly, 12-month clinical success rates are favorable but not different between both groups.

Abstract: The optimal management of patients with isolated posterior cerebral artery occlusion is uncertain. We compared clinical outcomes for endovascular therapy (EVT) versus medical management (MM) in patients with isolated posterior cerebral artery occlusion.This multinational case-control study conducted at 27 sites in Europe and North America included consecutive patients with isolated posterior cerebral artery occlusion presenting within 24 hours of time last well from January 2015 to August 2022. Patients treated with EVT or MM were compared with multivariable logistic regression and inverse probability of treatment weighting. The coprimary outcomes were the 90-day modified Rankin Scale ordinal shift and ≥2-point decrease in the National Institutes of Health Stroke Scale.Of 1023 patients, 589 (57.6%) were male with median (interquartile range) age of 74 (64-82) years. The median (interquartile range) National Institutes of Health Stroke Scale was 6 (3-10). The occlusion segments were P1 (41.2%), P2 (49.2%), and P3 (7.1%). Overall, intravenous thrombolysis was administered in 43% and EVT in 37%. There was no difference between the EVT and MM groups in the 90-day modified Rankin Scale shift (aOR, 1.13 [95% CI, 0.85-1.50]; P=0.41). There were higher odds of a decrease in the National Institutes of Health Stroke Scale by ≥2 points with EVT (aOR, 1.84 [95% CI, 1.35-2.52]; P=0.0001). Compared with MM, EVT was associated with a higher likelihood of excellent outcome (aOR, 1.50 [95% CI, 1.07-2.09]; P=0.018), complete vision recovery, and similar rates of functional independence (modified Rankin Scale score, 0-2), despite a higher rate of SICH and mortality (symptomatic intracranial hemorrhage, 6.2% versus 1.7%; P=0.0001; mortality, 10.1% versus 5.0%; P=0.002).In patients with isolated posterior cerebral artery occlusion, EVT was associated with similar odds of disability by ordinal modified Rankin Scale, higher odds of early National Institutes of Health stroke scale improvement, and complete vision recovery compared with MM. There was a higher likelihood of excellent outcome in the EVT group despite a higher rate of symptomatic intracranial hemorrhage and mortality. Continued enrollment into ongoing distal vessel occlusion randomized trials is warranted.

Abstract: Abstract Background Previous studies showed that the triglyceride-glucose (TyG) index was a better predictor of adverse cardiovascular events than triglycerides or fasting blood glucose alone. However, few studies have focused on new-onset hypertension. We aimed to explore the association of TyG index with new-onset hypertension in Chinese adults. Methods A total of 4,600 participants who underwent at least 2 rounds of visits from 2009 to 2015 in the China Health and Nutrition Survey were enrolled in this study. Our outcome of interest was new-onset hypertension. Multivariate Cox hazard regression models and restricted cubic spline were performed to explore the relationship between TyG index and new-onset hypertension. Results The mean (standard deviation, SD) age of the study population was 48.1 (13.6) years, and 2058 (44.7%) of the participants were men. The mean (SD) TyG index level was 8.6 (0.7). A total of 1,211 (26.3%) participants developed new-onset hypertension during a median (interquartile range) follow-up duration of 6.0 (2.0–6.1) years. The incidences of new-onset hypertension were 18.1%, 25.3%, 28.5%, and 33.4% by quartiles of TyG index [from quartile 1 (Q1) to Q4], respectively. The Cox model showed that high levels of TyG index were significantly associated with increased risk of new-onset hypertension (adjusted hazard ratio [aHR]: 1.29, 95% confidence interval [CI] 1.07–1.55, Q2; aHR, 1.24, 95% CI 1.03–1.49, Q3; aHR, 1.50, 95% CI 1.22–1.84, Q4) compared with Q1. Consistently, as a continuous variable, for every 1.0 increase in TyG index, there was a 17% increase in the risk of new-onset hypertension (aHR, 1.17; 95% CI 1.04–1.31). The associations were consistent in various subgroups and sensitivity analysis. The dose–response curve indicated a positive, linear association between TyG index and the risk of new-onset hypertension. Conclusions High TyG index was significantly associated with an increased risk of new-onset hypertension among Chinese adults. Our findings suggest that maintaining a relatively low level of TyG index might be effective in the primary prevention of hypertension.

Abstract: Abstract Aims This study aimed to report the long-term findings of the Italian programme of cardiovascular preparticipation screening (PPS) in young, competitive athletes. Methods and results The study assessed the diagnostic yield for diseases at risk of sudden cardiac death (SCD), the costs of serial evaluations, and the long-term outcomes of PPS in a large population of Italian children (age range, 7–18 years). The PPS was repeated annually and included medical history, physical examination, resting electrocardiogram, and stress testing; additional tests were reserved for athletes with abnormal findings. Over an 11-year study period, 22 324 consecutive children [62% males; mean age, 12 (interquartile range, 10–14) years at first screening] underwent a total of 65 397 annual evaluations (median 2.9/child). Cardiovascular diseases at risk of SCD were identified in 69 children (0.3%) and included congenital heart diseases (n = 17), channelopathies (n = 14), cardiomyopathies (n = 15), non-ischaemic left ventricular scar with ventricular arrhythmias (n = 18), and others (n = 5). At-risk cardiovascular diseases were identified over the entire age range and more frequently in children ≥12 years old (n = 63, 91%) and on repeat evaluation (n = 44, 64%). The estimated cost per diagnosis was 73 312€. During a follow-up of 7.5 ± 3.7 years, one child with normal PPS findings experienced an episode of resuscitated cardiac arrest during sports activity (event rate of 0.6/100.000 athletes/year). Conclusion The PPS programme led to the identification of cardiovascular diseases at risk of SCD over the whole study age range of children and more often on repeat evaluations. Among screened children, the incidence of sport-related cardiac arrest during long-term follow-up was low.

Abstract: Background: Depression and anxiety are two mental disorders that are often comorbid. However, the associations of long-term air pollution exposure with depression and anxiety remain inconclusive. Objective: We conducted a cross-sectional and prospective study to examine the associations of ambient exposure to particulate matter (PM) with a diameter of ≤2.5μm (PM2.5), ≤10μm (PM10), and 2.5–10μm (PMcoarse), nitrogen oxides (NOx), and nitrogen dioxide (NO2) with the risk of depression and anxiety in the UK Biobank. Methods: This study included 398,241 participants from the UK Biobank, 128,456 of whom participated the 7-y online mental health survey. A total of 345,876 individuals were free of depression and anxiety at baseline; of those, 16,185 developed incident mental disorders during a median of 8.7 y of follow-up. Depression and anxiety were assessed using hospital admission records and mental health questionnaires. Associations of air pollution with prevalent and incident mental disorders were examined using logistic regression and Cox regression models, respectively. Results: Elevated levels of the five air pollutants were associated with higher odds of mental disorders at baseline. Levels of four pollutants but not PMcoarse were also associated with higher odds and risks of mental disorders during follow-up; specifically, hazard ratios [HR, 95% confidence interval (CI)] of an interquartile range increase in PM2.5, PM10, NOx, and NO2 for incident mental disorders were 1.03 (95% CI: 1.01, 1.05), 1.06 (95% CI: 1.04, 1.08), 1.03 (95% CI: 1.01, 1.05), and 1.06 (95% CI: 1.04, 1.09), respectively. An air pollution index reflecting combined effects of pollutants also demonstrated a positive association with the risk of mental disorders. HR (95% CI) of incident mental disorders were 1.11 (95% CI: 1.05, 1.18) in the highest quintile group in comparison with the lowest quintile of the air pollution index. We further observed that the associations between air pollution and mental disorders differed by a genetic risk score based on single nucleotide polymorphisms previously associated with genetic susceptibility to mental disorders in the UK Biobank cohort. Discussion: To our knowledge, this research is one of the largest cohort studies that demonstrates an association between mental health disorders and exposure to long-term air pollution, which could be further enhanced by genetic predisposition. https://doi.org/10.1289/EHP10391

Abstract: Immune checkpoint inhibitors (ICIs) are approved for multiple cancers but can result in ICI-associated myocarditis, an infrequent but life-threatening condition. Elevations in cardiac biomarkers, specifically troponin-I (cTnI), troponin-T (cTnT), and creatine kinase (CK), are used for diagnosis. However, the association between temporal elevations of these biomarkers with disease trajectory and outcomes has not been established.We analyzed the diagnostic accuracy and prognostic performances of cTnI, cTnT, and CK in patients with ICI myocarditis (n=60) through 1-year follow-up in 2 cardio-oncology units (APHP Sorbonne: Paris, France and Heidelberg, Germany). A total of 1751 (1 cTnT assay type), 920 (4 cTnI assay types), and 1191 CK sampling time points were available. Major adverse cardiomyotoxic events (MACE) were defined as heart failure, ventricular arrhythmia, atrioventricular or sinus block requiring pacemaker, respiratory muscle failure requiring mechanical ventilation, and sudden cardiac death. Diagnostic performance of cTnI and cTnT was also assessed in an international ICI myocarditis registry.Within 72 hours of admission, cTnT, cTnI, and CK were increased compared with upper reference limits (URLs) in 56 of 57 (98%), 37 of 42 ([88%] P=0.03 versus cTnT), and 43 of 57 ([75%] P<0.001 versus cTnT), respectively. This increased rate of positivity for cTnT (93%) versus cTnI ([64%] P<0.001) on admission was confirmed in 87 independent cases from an international registry comprising 13 countries. In the Franco-German cohort, 24 of 60 (40%) patients developed ≥1 MACE (total, 52; median time to first MACE, 5 [interquartile range, 2-16] days). The highest value of cTnT:URL within the first 72 hours of admission performed best in terms of association with MACE within 90 days (area under the curve, 0.84) than CK:URL (area under the curve, 0.70). A cTnT:URL ≥32 within 72 hours of admission was the best cut-off associated with MACE within 90 days (hazard ratio, 11.1 [95% CI, 3.2-38.0]; P<0.001), after adjustment for age and sex. cTnT was increased in all patients within 72 hours of the first MACE (23 of 23 [100%]), whereas cTnI and CK values were less than the URL in 2 of 19 (11%) and 6 of 22 (27%) of patients (P<0.001), respectively.cTnT is associated with MACE and is sensitive for diagnosis and surveillance in patients with ICI myocarditis. A cTnT:URL ratio <32 within 72 hours of diagnosis is associated with a subgroup at low risk for MACE. Potential differences in diagnostic and prognostic performances between cTnT and cTnI as a function of the assays used deserve further evaluation in ICI myocarditis.

Abstract: Rationale: The respective effects of positive end-expiratory pressure (PEEP) and pressure support delivered through the helmet interface in patients with hypoxemia need to be better understood. Objectives: To assess the respective effects of helmet pressure support (noninvasive ventilation [NIV]) and continuous positive airway pressure (CPAP) compared with high-flow nasal oxygen (HFNO) on effort to breathe, lung inflation, and gas exchange in patients with hypoxemia (PaO2/FiO2 ⩽ 200). Methods: Fifteen patients underwent 1-hour phases (constant FiO2) of HFNO (60 L/min), helmet NIV (PEEP = 14 cm H2O, pressure support = 12 cm H2O), and CPAP (PEEP = 14 cm H2O) in randomized sequence. Measurements and Main Results: Inspiratory esophageal (ΔPES) and transpulmonary pressure (ΔPL) swings were used as surrogates for inspiratory effort and lung distension, respectively. Tidal Volume (Vt) and end-expiratory lung volume were assessed with electrical impedance tomography. ΔPES was lower during NIV versus CPAP and HFNO (median [interquartile range], 5 [3–9] cm H2O vs. 13 [10–19] cm H2O vs. 10 [8–13] cm H2O; P = 0.001 and P = 0.01). ΔPL was not statistically different between treatments. PaO2/FiO2 ratio was significantly higher during NIV and CPAP versus HFNO (166 [136–215] and 175 [158–281] vs. 120 [107–149]; P = 0.002 and P = 0.001). NIV and CPAP similarly increased Vt versus HFNO (mean change, 70% [95% confidence interval (CI), 17–122%], P = 0.02; 93% [95% CI, 30–155%], P = 0.002) and end-expiratory lung volume (mean change, 198% [95% CI, 67–330%], P = 0.001; 263% [95% CI, 121–407%], P = 0.001), mostly due to increased aeration/ventilation in dorsal lung regions. During HFNO, 14 of 15 patients had pendelluft involving >10% of Vt; pendelluft was mitigated by CPAP and further by NIV. Conclusions: Compared with HFNO, helmet NIV, but not CPAP, reduced ΔPES. CPAP and NIV similarly increased oxygenation, end-expiratory lung volume, and Vt, without affecting ΔPL. NIV, and to a lesser extent CPAP, mitigated pendelluft. Clinical trial registered with clinicaltrials.gov (NCT04241861).

Abstract: ABSTRACT Persistent high-risk human papillomavirus (HPV) infection is the pivotal cause of cervical carcinogenesis. HPV types distribution varies greatly by region, and its long-term changes of prevalence remain to be fully characterized in China. Here, the largest population of 198,111 consecutive women who underwent routine cervical screening were investigated from 2015 to 2021 in Guangzhou, south China. The results showed that the overall HPV prevalence was 21.66% (42,911/198,111), and the annual prevalence increased significantly from 2015 to 2021 (p < 0.001). HPV52, 16, 58, CP8304, 51, 53, 39, and 68 were the most prevalent HPV types. The relative HPV-positive rate correlated positively with the progression of cervical intraepithelial neoplasia (p < 0.001); HPV16 was the predominant carcinogenic type, followed by HPV52 and HPV18. HPV infections were significantly age-specific, and 26.51% (11,375/42,911) of cases were caused by multiple HPV types. In addition, HPV infections typically cleared over a median time of 16 (interquartile range 9–31) months, and the clearance of HPV16 was significantly faster than that of other types (p < 0.001). These findings may serve as a guide for local governments to evaluate HPV vaccination and cervical cancer prevention strategies in south China.

Abstract: Evidence for a potential link between air pollution and rheumatoid arthritis (RA) is inconsistent, and the modified effect of genetic susceptibility on the relationship between air pollution and RA has not been well studied.Using a general population cohort from the UK Biobank, this study aimed to investigate the associations between various air pollutants and the risk of incident RA and to further estimate the impact of combined exposure to ambient air pollutants on the risk of developing RA under the modification effect of genetic predisposition.A total of 342,973 participants with completed genotyping data and who were free of RA at baseline were included in the study. An air pollution score was constructed by summing the concentrations of each pollutant weighted by the regression coefficients with RA from single-pollutant models to assess the combined effect of air pollutants, including particulate matter (PM) with diameters ≤2.5μm (PM2.5), between 2.5 and 10μm (PM2.5-10), and ≤10μm (PM10), as well as nitrogen dioxide (NO2) and nitrogen oxides (NOx). In addition, the polygenic risk score (PRS) of RA was calculated to characterize individual genetic risk. The Cox proportional hazard model was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) of associations of single air pollutant, air pollution score, or PRS with incident RA.During a median follow-up time of 8.1 y, 2,034 incident events of RA were recorded. The HRs (95% CIs) of incident RA per interquartile range increment in PM2.5, PM2.5-10, PM10, NO2, and NOx were 1.07 (1.01, 1.13), 1.00 (0.96, 1.04), 1.01 (0.96, 1.07), 1.03 (0.98, 1.09), and 1.07 (1.02, 1.12), respectively. We also found a positive exposure-response relationship between air pollution score and RA risk (pTrend=0.000053). The HR (95% CI) of incident RA was 1.14 (1.00, 1.29) in the highest quartile group compared with the lowest quartile group of the air pollution score. Furthermore, the results of the combined effect of air pollution score and PRS on the RA risk showed that the risk of RA incidence in the highest genetic risk and air pollution score group was almost twice that of the lowest genetic risk and air pollution score group [incidence rate (IR) per 100,000 person-years: 98.46 vs. 51.19, and HR= 1.73 (95% CI: 1.39, 2.17) vs. 1 (reference)], although no statistically significant interaction between the air pollution and genetic risk for incident RA was found (pInteraction>0.05).The results revealed that long-term combined exposure to ambient air pollutants might increase the risk of RA, particularly in those with high genetic risk. https://doi.org/10.1289/EHP10710.

Abstract: BACKGROUND Despite newer treatments with immunosuppressive agents, there still exists a considerable morbidity and mortality risk among patients with antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV). Since 1994 the European Vasculitis Society (EUVAS) has aimed for an improved outcome for patients with AAV by several prospective randomized clinical trials (RCTs). The aim for the present study was to further evaluate the long-term survival of patients with AAV included in seven RCTs conducted by the EUVAS, as well as to identify potential prognostic factors. METHODS Long-term follow-up data were collected from questionnaires sent to the principal investigators of the original RCTs (1995-2012): MEPEX, NORAM, CYCAZAREM, CYCLOPS, IMPROVE, RITUXVAS and MYCYC, comprising 848 patients, all newly diagnosed with AAV. Relative survival estimates are presented for the study cohorts. Demographic, clinical and laboratory characteristics at trial entry were studied as potential prognostic factors in multivariable models. RESULTS 478 (56%) patients had Granulomatosis with polyangiitis (GPA) and 370 (44%) Microscopic polyangiitis (MPA) with a mean age at diagnosis of 58 ± 14 years. Median follow-up time was 8 years (IQR: 2.9-13.6). During the observation period, there were 305 deaths and the main causes were infections (26%), cardiovascular disease (14%) and malignancies (13%). When compared to a matched cohort, (regarding country, age-group, and sex) from the background population there was 14.2% more deaths among our cohort of AAV patients at 5 years, 19.9% at 10 years, 28.8% at 15 years and 36.3% at 20 years. The excess mortality occurred in all age groups. Estimated median survival time (from diagnosis) was 17.8 years (95%CI: 15.7-20). Among variables measured at baseline, advanced age, male sex, low estimated glomerular filtration rate, and low platelet count were identified as predictors of death in a multivariate Cox model. CONCLUSIONS Patients with AAV still have an increased risk of mortality compared to the general population despite newer therapeutic regimens. Treatment complications and organ damage are the main causes of limited survival, and infections remain the leading cause of mortality among patients with AAV.